The present project has ellucidated an animal model of experimental aminoglycoside nephrotoxicity in Fischer 3444 rats. This model reliably produces nonoliguric acute renal failure 7-10 days after a 40 mg/kg dose given twice daily. The illness is characterized by a decrease in glomerular filtration rate preceded by a urinary concentrating defect. This concentrating defect is found to be resistant to endogenous and exogenous antidiuretic hormone. In addition, the dosage regimen has an effect on toxicity. If the entire daily dose is divided into three doses, this is more nephrotoxic than if a single dose is administered. Thus, the height of the serum level can be dissociated from nephrotoxicity. The lesion is reversible despite continuation of the drug. Animals treated continuously with 40 mg/kg for 28 days recover functionally and morphologically from acute renal failure despite the continued presence of the drug. Current studies in progress are directed at the mechanism for this remarkable regenerative potential.